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Older Paternal Age Seen as Factor in Some Birth Defects

As men get older, their sperm deteriorates, a new study has found, and it is likely that the damaged sperm of older men is a significant factor in certain specific birth defects and in increasing the risk of abnormal pregnancies.

Birth rates since 1980 have increased by 40 percent in men 35 to 40 and decreased by 20 percent in men under 30, according to background information about the findings, published yesterday in The Proceedings of the National Academy of Sciences.

The rising age of fathers has been associated with reproductive problems including spontaneous abortion and with genetic diseases like achondroplasia, a type of dwarfism, and Apert syndrome, which involves severe bone malformations. Evidence from other studies also suggests that aging sperm plays a role in disorders like schizophrenia, in which genetic contributions to the illness are more complex and not as well understood. But little is known about which sperm abnormalities rise with age.

Using techniques that can detect DNA and chromosomal defects directly in sperm cells, the researchers examined the sperm of 97 healthy nonsmokers, ages 22 to 80. Compared with men in their 20's, those who were 40 to 49 had almost twice as much sperm DNA fragmentation, which is associated with failures of fertility, conception and sustained pregnancy.

"Our research suggests that men, too, have a biological time clock," said Brenda Eskenazi, one of two lead authors of the study and a professor of epidemiology at the School of Public Health at the University of California, Berkeley. "But men seem to have a gradual rather than an abrupt change in the potential to produce healthy offspring."

For the gene that causes dwarfism, researchers found a 2 percent increase in the frequency of the mutation for each year of increasing age. Those in their 40's were almost twice as likely as those in their 20's to produce sperm carrying the mutation. From age 60 to 80, the rate was more than three times as great as that of men in their 20's.

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Deteriorating sperm are associated with dwarfism and other disorders.Credit
John Walsh/Photo Researchers

Other kinds of genetic defects did not increase with age. Aneuploidy, the abnormal number of chromosomes that causes Down syndrome and various other genetic disorders, was no more common in the sperm of older men. Age made no difference in sex chromosome abnormalities, which can cause sterility and other physical or mental problems.

In contrast with findings in a previous study that used similar techniques, the researchers found no evidence that the mutation that causes Apert syndrome was any more common in older men's sperm than in that of younger men. Andrew J. Wyrobek, the study's other lead author, said that these varying findings from different groups of men raised the possibility that something more than age was involved.

Economic status, ethnic background and diet may cause differing responses to aging, and those differences may then be reflected in sperm characteristics.

Factors like quantity of semen, sperm concentrations and total sperm count were not associated with any genomic defects, but sperm motility was associated with increased DNA fragmentation.

No association was found between age and sperm sex ratio, so older men are no more or less likely to have girl or boy babies than their younger counterparts.

Dr. Wyrobek, a senior staff scientist at the Lawrence Berkeley National Laboratory, said that an immense amount of work remained to be done.

"There are more than 30,000 genes and we've only measured the effects on age of two of them in sperm," he said. "Many gene mutations in sperm can cause genetic diseases in children, and these still need to be measured in older men, but we don't have the tools yet."

A version of this article appears in print on , on page F6 of the New York edition with the headline: Older Paternal Age Seen as Factor in Some Birth Defects. Order Reprints|Today's Paper|Subscribe